Boyd-White J, Williams J C
Molecular and Cellular Pathobiology Program, Medical University of South Carolina, USA.
Diabetes. 1996 Mar;45(3):348-53. doi: 10.2337/diab.45.3.348.
There is much evidence that basement membranes, such as in the renal glomerulus, act as macromolecular sieves, restricting the passage of proteins. Cross-linking of matrix proteins, as occurs because of advanced glycosylation end products (AGEs) in diabetes, may have an effect on the sieving properties of the basement membrane. To test this hypothesis, Matrigel, a basement membrane-like matrix, was cross-linked with glycolaldehyde and control and cross-linked matrices compared. Control matrices allowed less bovine serum albumin to pass through than did cross-linked matrices, with sieving coefficients (SCs) of 0.38 +/- 0.02 and 0.52 +/- 0.02, respectively (P < 0.0005). The control matrices also allowed less cross-linked albumin through than did the cross-linked matrices: 0.13 +/- 0.01 vs. 0.17 +/- 0.02 (P < 0.002). The SCs of a series of fluorescein isothiocyanate dextrans (four sizes, Mr 16,000- 168,000) were lower for the control matrix than for the cross-linked matrix (P < 0.03). In addition, the SC for glycated albumin (incubated with glucose-6-phosphate) was higher than that of normal albumin for both the control (P < 0.04) and cross-linked matrices (P < 0.001). These data indicate that cross-linking of the matrix increases permeability to macromolecules. Analysis of the data using fiber-matrix theory suggests that the mean fiber radius was increased in the cross-linked matrix. The data also indicate that glycated albumin filters through the matrices more easily than does normal albumin. In relation to the situation seen in vivo, it is possible that glycation of circulating proteins and AGE modification of glomerular basement membrane proteins may both contribute to the proteinuria seen in diabetes.
有大量证据表明，诸如肾小体中的基底膜可作为大分子筛，限制蛋白质的通过。基质蛋白的交联，如糖尿病中晚期糖基化终产物（AGEs）所导致的交联，可能会影响基底膜的筛分特性。为了验证这一假设，将基质胶（一种基底膜样基质）与乙醇醛交联，并对对照基质和交联基质进行比较。对照基质比交联基质允许更少的牛血清白蛋白通过，筛分系数（SCs）分别为0.38±0.02和0.52±0.02（P<0.0005）。对照基质比交联基质允许通过的交联白蛋白也更少：0.13±0.01对0.17±0.02（P<0.002）。一系列异硫氰酸荧光素葡聚糖（四种大小，Mr 16,000 - 168,000）在对照基质中的SCs低于交联基质（P<0.03）。此外，糖化白蛋白（与6 - 磷酸葡萄糖孵育）在对照基质（P<0.04）和交联基质（P<0.001）中的SCs均高于正常白蛋白。这些数据表明基质的交联增加了对大分子的通透性。使用纤维 - 基质理论对数据进行分析表明，交联基质中的平均纤维半径增加。数据还表明，糖化白蛋白比正常白蛋白更容易通过基质。就体内所见情况而言，循环蛋白的糖基化和肾小球基底膜蛋白的AGE修饰都可能导致糖尿病中出现的蛋白尿。
